Search Results (3,478)

Amino alcohols are a class of compounds bearing both amino and hydroxyl groups, ubiquitous in natural products and extensively utilized as key structural motifs in pharmaceuticals and functional materials. Owing to their structural diversity, inherent chirality, and high reactivity, they exhibit significant application value in the pharmaceutical field, materials industry, and organic synthesis. Compared with chemical synthesis, which suffers from limitations such as insufficient enantioselectivity, dependence on precious metal catalysts, and environmental concerns, biosynthesis offers core advantages of high stereoselectivity, mild reaction conditions, and environmental sustainability. This review systematically delineates the diverse applications of amino alcohols in the pharmaceutical field (e.g., anti-HIV, antimalarial, and antitumor drugs), materials industry (e.g., polymer modification and metal corrosion protection), and organic synthesis (e.g., chiral ligands and catalysts). Particular emphasis is placed on the biosynthetic strategies and pathways of representative amino alcohols, including ethanolamine, (2S,3R)-2-amino-1,3,4-butanetriol, (R)-3-amino-1-butanol, sphingosine, and metaraminol, as well as the metabolic engineering design principles and downstream processing technologies for amino alcohol biosynthesis. Although current biosynthetic approaches still face bottlenecks in enzyme catalytic efficiency, substrate tolerance, cofactor regeneration, product toxicity, and thermodynamic equilibrium, substantial improvements in synthetic efficiency and stereoselectivity have been achieved through protein engineering, metabolic engineering, in situ product removal, and multi-enzyme cascade optimization. This review aims to provide systematic theoretical references and technical insights for the green and efficient biomanufacturing of amino alcohols. Full article

The influence of natural and synthetic blue food colorants on the human body, including the cardiovascular system, is a complex and not fully understood topic. Considering that various papers have demonstrated that oxidative stress is a crucial step in the development of cardiovascular diseases (CVDs), our experiments on the pro- or antioxidant action of three blue food colorants (one natural colorant—genipin—and two synthetic colorants—brilliant blue FCF and patent blue V) focused on two aspects that are important for the development of CVDs: the level of biomarkers of oxidative stress induced by H₂O₂/Fe²⁺ (the donor of hydroxyl radicals—one of the most aggressive reactive oxygen species produced in humans) in human blood platelets and human plasma, as well as the arachidonic acid cascade in blood platelets stimulated by thrombin (in vitro). Our results demonstrated that two tested blue colorants—genipin and brilliant blue FCF (at four used concentrations: 2, 10, 20, and 200 µM)—reduced plasma lipid peroxidation induced by H₂O₂/Fe²⁺. Moreover, all tested blue colorants (genipin, brilliant blue FCF, and patent blue V; at the concentrations 2, 10, 20, and 200 µM) inhibited lipid peroxidation in blood platelets treated with H₂O₂/Fe²⁺. In contrast, only genipin (at the highest used concentration—200 µM) statistically significantly reduced plasma protein carbonylation induced by H₂O₂/Fe²⁺ (inhibition of this process: about 25%). However, all tested food colorants decreased blood platelet protein carbonylation stimulated by H₂O₂/Fe²⁺, but their action was not always statistically significant. In addition, we noted that all used blue food colorants (1–200 µM) have protector effects on the change in the level of thiol groups in plasma proteins stimulated by H₂O₂/Fe²⁺, but these tested colorants change the level of thiol groups in blood platelets treated with H₂O₂/Fe²⁺ only at the highest used concentration—200 µM. In conclusion, the present study provides the first data on the antioxidant potential of genipin, brilliant blue FCF, and patent blue V in selected elements of blood treated with H₂O₂/Fe²⁺. Earlier and current studies have indicated the promising potential of these blue food colorants, especially genipin (without cytotoxicity toward human blood platelets), which can modify the oxidative stress of platelets and plasma in vitro at concentrations (1–200 µM) which can be obtained in blood during its administration. However, the presented results have limitations, especially concerning the mechanistic clarity surrounding the antioxidant properties of the tested blue food colorants. Therefore, further in vivo experiments are needed to provide a better understanding of their antioxidant potential. Full article

Retroviruses induce immunosuppression in their infected hosts. This phenomenon is well described for the immunodeficiency viruses, with human immunodeficiency virus type 1 (HIV-1) representing the best-studied example, but it also occurs in other retroviral infections. Immunosuppressive properties were first characterized in murine leukemia viruses (MuLV). Additional well-studied examples include feline leukemia virus (FeLV) and koala retrovirus (KoRV). Investigations into the mechanisms underlying retrovirus-induced immunosuppression revealed that not only inactivated viral particles but also their purified transmembrane (TM) envelope proteins exhibit immunosuppressive activity. However, in certain retroviral infections, additional viral proteins contribute to the immunosuppression in vivo. Within the TM envelope proteins, a highly conserved region—designated the immunosuppressive (isu) domain—was identified. Synthetic peptides corresponding to this domain suppress a wide range of in vitro immune responses, possibly by regulating Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR pathways. They modulate cytokine release and alter gene expression in immune cells, mirroring the activity of the corresponding TM envelope protein. Mutations in the sequence abrogate the effect. Numerous TM envelope proteins have demonstrated immunosuppressive activity in vivo in a tumor rejection model, and mutations within the isu domain also abrogate this function. These studies have important implications for reproduction, particularly through the immunosuppressive syncytins in the placenta, for tumor development, where similar mechanisms may protect cancer cells from the host immune system, and for vaccine development and xenotransplantation. Notably, immunization with TM envelope proteins carrying mutations in the isu domain elicits stronger immune responses compared with the wild-type proteins. Finally, the potential of retroviral TM envelope proteins to protect xenotransplants from immune rejection will be discussed. Full article

Natural coumarins are a structurally privileged group of bioactive benzopyranone lactones widely spread across the Apiaceae, Rutaceae, and Leguminosae families, and hold significant potential as inhibitors of pathological protein aggregation in Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes mellitus. The fully planar, rigid bicyclic structure of the coumarin nucleus (~3.4–3.5 Å thickness) is geometrically compatible with intercalative π–π stacking with aggregation-nucleating aromatic residues, including Phe19 of Aβ(1–42), providing a mechanistically coherent pharmacophoric basis for anti-aggregation activity according to computational and indirect biophysical evidence. This review critically evaluates the peer-reviewed literature on naturally occurring coumarins and their synthetic derivatives as candidate β-sheet intercalators, with analysis of SAR at C-3 to C-8 positions; multi-target-directed ligand designs with dual activities of inhibiting AChE, BACE-1, GSK-3β, and MAO-B, and as blood–brain barrier-penetrating neuroprotective agents validated in cellular and rodent models. The critical analysis identifies the translational gap between in vitro IC₅₀ values and attainable brain drug concentrations as the primary pharmacological obstacle. It identifies the absence of systematic investigation of coumarin against IAPP, a directly relevant amyloid target in metabolic neurodegeneration, as the most significant unmet research priority in the field. Full article

Synthetic polymers are commonly incorporated into natural polymer nanofibers to enhance their overall performance. In this study, we investigated the effects of different poly(vinyl alcohol) (PVA) concentrations (0%, 2.5%, 5%, 7.5%, and 10% w/v) on the properties of gelatin/zein nanofibers. With increasing PVA concentration, fiber diameter significantly decreased from 976 ± 165 nm to 262 ± 60 nm, followed by a gradual increase to 396 ± 81 nm, indicating that PVA plays a crucial role in fiber diameter regulation. At higher concentrations (7.5% and 10% w/v), PVA became dominant, inducing protein aggregation and porous channel formation, which in turn increased the water vapor permeability of the composites. Rheological and mechanical analyses revealed that at these concentrations, the composites exhibited enhanced flexibility while maintaining network stability, demonstrating strong application potential. Furthermore, PVA incorporation induced a slight increase in the primary decomposition temperature (from 320.77 °C to 328.67 °C), indicating enhanced intermolecular compatibility and restricted segmental mobility within the protein–PVA network. Overall, these results establish a theoretical basis for tailoring fiber architecture and interfacial compatibility in natural–synthetic polymer composites. Further, the structural attributes of the resulting fibrous mats indicate their potential for food processing applications beyond conventional food packaging, including use as filtration media. Full article

Triple-negative breast cancer (TNBC), particularly when associated with breast cancer susceptibility gene 1/2 (BRCA1/2) alterations or homologous recombination deficiency (HRD), remains therapeutically challenging because DNA repair vulnerabilities coexist with molecular heterogeneity, resistance, and toxicity constraints. This narrative review synthesizes mechanistic, preclinical, clinical, and translational evidence on DNA damage response (DDR)-targeted and synthetic lethality-based strategies in TNBC. We summarize TNBC biological heterogeneity, current biomarker-guided treatment options, mechanisms of poly(ADP-ribose) polymerase (PARP) inhibition and resistance, and emerging DDR targets, including ataxia telangiectasia and Rad3-related/checkpoint kinase 1 (ATR/CHK1), WEE1, DNA-dependent protein kinase (DNA-PK), RAD51, DNA polymerase theta (POLQ), neddylation-related pathways, and targeted protein degradation. The review highlights that PARP inhibitors and platinum agents provide clinically validated examples of exploiting HRD in selected populations, whereas most next-generation DDR inhibitors remain preclinical, investigational, or in early clinical trials. Resistance mechanisms, including BRCA reversion, homologous recombination restoration, replication fork stabilization, and checkpoint adaptation, limit durable benefit. Safety, target selectivity, overlapping toxicities, and the lack of standardized functional biomarkers further constrain translation. Future progress will require prospective biomarker validation, dynamic HRD assessment, rational scheduling of combinations, and medicinal chemistry approaches that improve therapeutic index rather than a broad application of DDR inhibition across all TNBC. Full article

Natural products like the isoprenylated flavonoid Kuwanon G (KWG), isolated primarily from Morus alba, offer promising pleiotropic effects against multifactorial diseases, overcoming the limitations of conventional single-target synthetic drugs. This study aims to systematically review the pharmacological activities of KWG and evaluate its underlying molecular mechanisms. A comprehensive literature review was integrated with network pharmacology, protein–protein interaction (PPI) profiling, and KEGG/GO pathway enrichment analyses to identify shared targets across different pathologies. Experimental data demonstrate that KWG exhibits antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, anti-obesity, and anticancer properties. Bioinformatics analyses revealed that KWG exerts these effects by modulating core targets (e.g., TNF, IL-6, SRC, RELA) and key signaling pathways, including NF-κB, PI3K/AKT/mTOR, and Toll-like receptors, which govern inflammation, oxidative stress, and metabolic regulation. In conclusion, KWG is a potent, multi-target compound with significant therapeutic potential for managing chronic and infectious diseases. However, future structure–activity relationship studies and clinical trials are required to address its pharmacokinetic limitations, such as low bioavailability, to facilitate its clinical translation. Full article

The protective effect of arzanol, a natural prenylated phloroglucinol α-pyrone from the Helichrysum microphyllum subsp. tyrrhenicum, was investigated in HaCaT keratinocytes exposed to two inflammatory stimuli: lipopolysaccharide (LPS, 0.5–75 µg/mL), a component of gram-negative bacteria, and polyriboinosinic-polyribocytidylic acid (poly I:C, 0.5–50 µg/mL), a synthetic viral RNA analog. LPS and poly I:C significantly decreased HaCaT cell viability (18–93% reduction in the 5–75 μg/mL LPS range and 25% at 50 μg/mL poly I:C, MTT assay) and increased apoptosis and cell death (NucView 488 and propidium iodide assay) after 3 h and 24 h of exposure. Arzanol (1 h of pre-incubation, 5–25 μM) showed a significant protective effect against LPS and poly I:C-induced damage, preserving cell viability (25% of viability increase at 5 μg/mL LPS concentration, and 30% at 50 μg/mL of poly I:C) and decreasing apoptosis/cell death. Western blot analysis demonstrated the ability of arzanol (5 μM) to reduce the apoptotic protein Bax and the inflammatory cytokine IL-1β levels in HaCaT keratinocytes exposed for 3 h to 5 and 10 μg/mL LPS. Moreover, scratch assay showed the arzanol reparative effect on HaCaT cells. Our results qualified arzanol as a protective drug for dermatological applications in human skin diseases. Full article

Folate is an essential vitamin associated with protein and DNA synthesis in the body. Compared with synthetic folic acid, 6S-5-methyltetrahydrofolate calcium salt crystal form C (MTHF CAC) is safer and has a higher bioavailability. In this study, a nanofiber membrane (MT-GE) was prepared from fish gelatin and MTHF CAC in the aqueous system via electrospinning. Differential scanning calorimetry showed higher transition temperatures for MT-GE than for GE. The weight loss curve of MT-GE detected by thermogravimetric analysis was higher than that of GE. The results corresponded to those of X-ray diffraction, which indicated the slightly higher crystalline strength of MT-GE than GE. Therefore, the inclusion of MTHF CAC improved the physical characteristics of GE nanofibers. High-performance liquid chromatography analysis revealed that the retention of MTHF CAC in MT-GE reached 85.57%, which suggested that electrospinning caused no effect on the properties of MTHF CAC. The MT-GE membrane supported cell proliferation, and the Cell Counting Kit-8 results indicated that the cell proliferation rate exceeded 100%, with the MT-GE solution demonstrating more than double the proliferation rate of the control group. Therefore, MT-GE has great potential for use as a medical biomaterial. Full article

Antimicrobial resistance and persistent biofilm-associated infections have renewed interest in bacteriophages as alternatives or complements to conventional antibiotics. However, broader therapeutic adoption remains constrained by slow phage discovery, incomplete genome characterization, narrow host range, complex therapeutic matching, and manufacturing variability. Artificial intelligence (AI) offers computational approaches that may help address several of these limitations. This comprehensive narrative review discusses current AI applications across the bacteriophage pipeline, including metagenomic phage discovery, genome annotation, phage–host interaction prediction, personalized phage selection, cocktail optimization, and phage–antibiotic combination design. The review also examines AI-assisted synthetic biology approaches, including receptor-binding protein redesign, CRISPR-enabled engineering, generative genome design, and biosafety screening, as well as emerging applications in bioprocess optimization, yield prediction, purification analytics, quality assurance, and supply-chain management. Current evidence suggests that AI may accelerate phage identification, improve host-range prediction, support therapeutic optimization, and strengthen manufacturing consistency, potentially facilitating the transition of phage therapy from individualized rescue interventions toward more scalable antimicrobial platforms. Nevertheless, major limitations remain, including fragmented, taxonomically biased datasets; limited external validation; restricted interpretability; privacy concerns; biosafety oversight; and evolving regulatory frameworks. Future progress will depend on standardized datasets, multimodal validation, scalable manufacturing systems, experimental and clinical verification, and coordinated regulatory development. Full article

Background/Objectives: The double-strand break repair protein MRE11 forms the core of the MRE11/RAD50/NBS1 (MRN) complex. Cancers with reduced MRE11 expression have been suggested to be more sensitive to radio-chemotherapy and may be subject to synthetic lethality. The aim of this study was to assess the prevalence of MRE11 deficiency and the potential role and clinical significance of elevated and/or reduced MRE11 expression in human cancer. Methods: A tissue microarray containing 14,966 samples from 134 different tumor entities was analyzed for MRE11 by immunohistochemistry. Results: In normal tissues, strong nuclear MRE11 staining occurred in almost all cell types. In cancers, nuclear MRE11 staining was strong in 11,797 (91.0%), moderate in 1018 (7.9%), weak in 86 (0.7%), and completely absent (MRE11 deficiency) in 55 (0.4%) of 12,956 informative tumor samples. Only six tumor entities had more than one MRE11-deficient cases including hepatocellular carcinoma (9 of 193), intestinal type gastric adenocarcinoma (4 of 208), endometrioid endometrial carcinoma (5 of 268), pulmonary adenocarcinoma (2 of 165), colorectal adenocarcinoma (CRC, 16 of 2183), and clear cell renal cell carcinoma (ccRCC, 7 of 1011). Reduced MRE11 staining was associated with mismatch repair deficiency (dMMR) in CRC and in gastric adenocarcinoma (p < 0.0001 each), advanced pT stage (p = 0.0003) and L1 status (p = 0.0019) in testicular seminoma, high grade (p < 0.05), advanced pT (p < 0.0001), and high UICC stage (p = 0.0014) in ccRCC, advanced pT stage in high-grade serous ovarian carcinoma (p = 0.0396), and nodal metastases in papillary thyroid cancer (p = 0.0332). Conclusions: MRE11 is highly expressed in most cancers. Reduced MRE11 expression is associated with aggressive phenotype in multiple cancer types. The potential to exploit MRE11 deficiency as a target for synthetic lethality deserves to be further explored. Full article

Plant cytochrome P450 monooxygenases (CYPs) are valuable biocatalysts for the regioselective hydroxylation of aromatic compounds. However, their expression in bacterial hosts is hampered by poor solubility, membrane anchoring and the requirement for redox partners. In this work, we report the design and characterization of modular expression systems that enable the functional production of SbCYP82D1.1 from Scutellaria baicalensis (SbF6H) in Escherichia coli. Both independent expression and synthetic fusion systems were evaluated by combining a CYP with a compatible reductase (ATR2_tr from Arabidopsis thaliana) to catalyze the conversion of chrysin into baicalein. A combinatorial library of N-terminal variants, host strains, media, and induction strategies was constructed and screened. Among the tested host, E. coli DH 10-beta provided the highest product titers, particularly when cultures were supplemented with 5-aminolevulinic acid. Truncation of the native transmembrane anchor significantly improved catalytic performance, whereas the addition of the heterologous MALLLAVF tag decreased activity. Fusion systems outperformed separate expression formats, showing approximately two-fold higher activity, with the flexible glycine–serine linker (L_GS) supporting the highest hydroxylation product formation. The corresponding fusion construct showed an apparent conversion of 0.1 mM chrysin to baicalein of up to 90% under the applied whole-cell reaction and analytical conditions, although this value should be interpreted with caution due to the concurrent instability of baicalein observed in all reactions and culture conditions. This result nevertheless indicates a marked improvement in whole-cell baicalein formation compared with previously reported bacterial systems. Together, these results demonstrate that rational N-terminal engineering combined with fusion protein design can enable efficient bacterial expression of plant CYPs, representing a promising step toward scalable production of hydroxylated flavonoids. Full article

Generative artificial intelligence (AI) is transforming biological and medical research and data analysis. Beyond analyzing existing information, these models can learn complex patterns and generate new data such as realistic protein sequences, genetic variants, or clinical notes. In molecular biology, language-like sequence models can read and generate DNA, RNA, and amino acid sequences to predict genetic variant effects, design new proteins, and explore molecular functions. In medicine, large language models (LLMs) trained on biomedical literature and electronic health records (EHRs) can summarize clinical findings, identify patterns, and provide decision support for clinicians and healthcare providers. Additionally, synthetic data generation can help protect patient privacy and augment existing disease datasets. While these advances make tasks that were previously impractical possible at scale, they also carry major risks, including producing convincing but incorrect results, reflecting hidden biases in the training data, and underperforming when real-world conditions change. Full article

Polymer coatings are integral to nearly every modern cardiovascular and endovascular device, including drug-eluting stents (DESs) and drug-coated balloons (DCBs), bioabsorbable vascular scaffolds (BVSs), occluders, grafts, and catheter and guidewire hydrophilic surfaces. Persistent complications, including late stent thrombosis, delayed endothelialization, hypersensitivity, and restenosis, show that coatings actively shape biological responses rather than acting as inert drug carriers. Their surface chemistry, drug release kinetics, and degradation behavior are upstream determinants of blood– and tissue–material responses that govern healing and failure. This review frames coating selection as a structure–property–biological response problem. It surveys the major classes of synthetic polymer coatings and the defining surface and bulk properties. This review also examines how composition and architecture control drug release, and traces the interfacial cascade of protein adsorption, coagulation and complement activation, platelet and leukocyte responses, and neutrophil extracellular trap (NET) formation. These mechanisms are linked to contemporary design strategies that improve hemocompatibility, limit thrombosis, promote endothelial recovery, and tune degradation, and to the standardization and translation gaps that remain. The central message is that polymer coatings are not biologically equivalent. Their surface chemistries and degradation profiles determine the thrombo-inflammatory outcomes. Therefore, coating design should be guided by intended biological response, not drug release alone. Full article

Background/Objectives: Mosquitoes, including Culex quinquefasciatus and Aedes aegypti, are important vectors of dengue fever, Zika virus, West Nile virus, Japanese encephalitis virus, Eastern equine encephalitis virus, etc. Biological control has always been urgent in mosquito prevention due to resistance developing to synthetic insecticides and environmental toxicity by insecticides. Methods: The leaf essential oil of Mosla. chinensis was isolated, and major components were identified via GC-MS, followed by olfactory behavior assays to evaluate its repellent activity against C. quinquefasciatus. Additionally, the odorant-binding protein 1 and odorant-binding protein 2 (CquiOBP1-2) genes were prokaryotically expressed, and their fluorescence competitive binding activities with the active components of essential oils were examined. Results: The bioassays indicated this essential oil greatly repels C. quinquefasciatus, which will significantly protect people against vector-borne diseases. In the fluorescence competitive binding experiments, the CquiOBP1-2 proteins exhibit great binding capacities to volatile components, including Citronellal, Citronellol, Geraniol, Limonene and Isopulegol. Furthermore, the behavioral experimental results also indicate that the mixture of these five ligand compounds has an obvious repellent effect on mosquitoes, highlighting that they may be applied as potential mosquito repellent agents. Moreover, molecular docking and site-directed mutation analysis further confirm Phe123 and Gln77 are both key amino acid residues of CquiOBP1-2 proteins involved in the olfactory recognition of repellent ligand compounds from M. chinensis essential oil. Conclusions: The behavioral experimental verification and the exploration of olfactory molecular mechanisms are helpful to promote the biological control of plant essential oils in mosquito pests. Full article